Tolerogenic modulation of the immune response by oligoglycerol- and polyglycerol-peptide conjugates

Bioconjugate Chemistry
Shilpi GuptaRainer Haag

Abstract

Peptide-based therapy is a promising strategy for antigen-specific immunosuppression to treat or even heal autoimmune diseases with significantly reduced adverse effects compared to conventional therapies. However, there has been no major success due to the drawbacks of native peptides, i.e., limited bioavailability. Considering the importance and limitations of peptide-based therapies for treatment of autoimmune diseases, we designed and constructed oligoglycerol (OG)- and polyglycerol (PG)-based peptide conjugates. They were evaluated for their biological activity (in vitro and in vivo), bioavailability, and tolerogenic potential. Among the OG- and PG-peptide constructs, PG-peptide constructs exhibited an extended bioavailability compared to OG-peptide constructs and unconjugated peptide. Interestingly, size, structure, and linker chemistry played a critical role for the tolerogenic capacity of the constructs. The PG-peptide construct bound via an ester linkage was the most tolerogenic conjugate, while the PG-peptide construct bound via an amide induced stronger proliferation, but also higher TNF production and lower frequencies of Foxp3(+) regulatory T-cells. Therefore, we conclude that PG-peptide conjugates bound via an est...Continue Reading

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Citations

Aug 16, 2016·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Fabiola PuentesOlaf Rötzschke
Mar 11, 2016·Chemistry : a European Journal·Sumit KumarChristoph Böttcher
Dec 21, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Srinivas AbbinaJayachandran N Kizhakkedathu
Nov 10, 2020·Frontiers in Immunology·Jennifer PfeilUte Hoffmann
Aug 20, 2021·Therapeutic Advances in Chronic Disease·Jennifer PfeilAlf Hamann

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